P53 family members regulate the Otx1 gene expression in differentiation of breast cancer stem cells and in mammary gland development.

Tp53, Tp63 and Tp73 family members encode for transcription factors which play a key role in control of the genome integrity inducing cell-cycle arrest, senescence, apoptosis or cell differentiation. They take a part in cell stress response and in tumor suppression (De Young MP and Ellisen LW, 2007). Wild type p53 protein is a growth modulator and its inactivation is a critical event in malignant transformation (Gasco M, 2002). It has been recently demonstrated that p53 has developmental and differentiation functions (Hu W, 2008). Indeed an over-expression of p53 in tumor cells induces asymmetrical division avoiding a self-renewal of cancer stem cells (CSCs) and promoting their differentiation (Cicalese A, 2009). In this study 43 human ductal and lobular invasive breast carcinomas have been analyzed for the expression of p53, p63, p73 and a pool of non-clustered homeobox genes. The homeogenes play a crucial role in embryogenesis, regulating cell differentiation and proliferation (Pagani IS, 2010). They are expressed in adult mammary gland and when deregulated, are involved in breast cancer (Lewis MT, 2000). We demonstrated that the Otx1 homeogene is transcribed in breast cancer, in CSCs differentiation and in adult mammary gland development. We established that the p53 and p73 proteins directly induce the Otx1 expression by acting on its promoter. Otx1 has been described as a critical molecule for axon refinement in corticogenesis (Zhang YA, 2002), and its activity in breast cancer suggests a synergistic function with p53 and p73 in CSCs differentiation. In adult mammary gland development the Otx1 expression is not regulated by p53, but is correlated with the expression of Tp73 in lactation and in regression. This suggests that in physiological conditions Otx1 is regulated by p73, while in the tumors p53 regulates its expression

P53 family members regulate the Otx1 gene expression in differentiation of breast cancer stem cells and in mammary gland development.

Tp53, Tp63 and Tp73 family members encode for transcription factors which play a key role in control of the genome integrity inducing cell-cycle arrest, senescence, apoptosis or cell differentiation. They take a part in cell stress response and in tumor suppression (De Young MP and Ellisen LW, 2007). Wild type p53 protein is a growth modulator and its inactivation is a critical event in malignant transformation (Gasco M, 2002). It has been recently demonstrated that p53 has developmental and differentiation functions (Hu W, 2008). Indeed an over-expression of p53 in tumor cells induces asymmetrical division avoiding a self-renewal of cancer stem cells (CSCs) and promoting their differentiation (Cicalese A, 2009). In this study 43 human ductal and lobular invasive breast carcinomas have been analyzed for the expression of p53, p63, p73 and a pool of non-clustered homeobox genes. The homeogenes play a crucial role in embryogenesis, regulating cell differentiation and proliferation (Pagani IS, 2010). They are expressed in adult mammary gland and when deregulated, are involved in breast cancer (Lewis MT, 2000). We demonstrated that the Otx1 homeogene is transcribed in breast cancer, in CSCs differentiation and in adult mammary gland development. We established that the p53 and p73 proteins directly induce the Otx1 expression by acting on its promoter. Otx1 has been described as a critical molecule for axon refinement in corticogenesis (Zhang YA, 2002), and its activity in breast cancer suggests a synergistic function with p53 and p73 in CSCs differentiation. In adult mammary gland development the Otx1 expression is not regulated by p53, but is correlated with the expression of Tp73 in lactation and in regression. This suggests that in physiological conditions Otx1 is regulated by p73, while in the tumors p53 regulates its expression

Bystander intervention among secondary school pupils: testing an augmented Prototype Willingness Model

This study augmented the Prototype Willingness Model (PWM) to assess reactive and deliberative decision-making underpinning bystander intervention in gender-based violence contexts. There were 2079 participants (50% male, 49% female, 1% unreported), aged 11-15-years-old (M = 12.32, SD = 0.91), attending 19 secondary schools across Scotland. Participants self-reported the augmented PWM variables, then their intervention behaviour approximately one month later. Path analyses mostly supported the predicted relationships between positive and negative bidimensional attitudes, subjective norms, prototype perceptions, perceived behavioural control, and self-efficacy on intentions and willingness. Willingness predicted positive (speaking with a teacher) and negative (doing nothing) intervention in less serious violence. Self-efficacy predicted negative intervention in more serious violence. Subjective norms positively moderated the attitudes-intentions relationship. Overall, the results suggested that reactive (willingness) more so than deliberative (intention) decision-making account for intervention when young people witness gender-based violence. Additionally, the findings highlight the complexity of bystander intervention decision-making, where adding control perceptions, bidimensional attitudes, and moderators have independent contributions. Furthermore, self-comparison to the typical bystander who positively intervenes (prototype perceptions) was the strongest predictor of intentions and willingness, highlighting in a novel way the importance of image, and group membership on decision-making

The C-terminal domain of yeast Ero1p mediates membrane localization and is essential for function

AbstractIn eukaryotes, members of the Ero1 family control oxidative protein folding in the endoplasmic reticulum (ER). Yeast Ero1p is tightly associated with the ER membrane, despite cleavage of the leader peptide, the only hydrophobic sequence that could mediate lipid insertion. In contrast, human Ero1-Lα and a yeast mutant (Ero1pΔC) lacking the 127 C-terminal amino acids are soluble when expressed in yeast. Neither Ero1-Lα nor Ero1pΔC complements an ERO1 disrupted strain. Appending the yeast C-terminal tail to human Ero1-Lα restores membrane association and allows growth of ERO1 disrupted cells. Therefore, the tail of Ero1p mediates membrane association and is crucial for function